lithoheterotrophic

METPO:1000648 · CLASS · REVIEWED

A trophic type in which an organism obtains energy from the oxidation of inorganic compounds while using organic compounds as the primary carbon source for biosynthesis.

Trait evidence (2)

DOI:10.1038/s41598-021-81412-3
engineered lithoheterotrophic strain

Experimental study supports Fe(II)-dependent lithoheterotrophic growth with glucose as carbon source.
DOI:10.1016/B978-0-12-378630-2.00219-X
oxidize inorganic atoms or molecules

Review supports inorganic compound oxidation as lithotrophic energy metabolism.

Lithoheterotrophic inorganic energy and organic carbon use

DOI-backed graph linking inorganic electron donors, Fe(II) oxidation, respiratory energy conservation, organic carbon uptake, precursor metabolites, and biomass.

MECHANISTIC · This modular graph covers Fe(II), reduced-sulfur, H2, and an exploratory direct-electron-transfer branch. The S. alaskensis example anchors only aerobic H2-supported growth on organic carbon; Q1J422 is one hydrogenase large subunit, not the complete complex or evidence for every donor branch.

Edge evidence

lithoheterotrophic has electron donor inorganic electron donor METPO:2007701
Inorganic compounds serve as the energy-generating electron donors for lithoheterotrophy.
- DOI:10.1016/B978-0-12-378630-2.00219-X oxidize inorganic atoms or molecules Supports inorganic chemical oxidation as lithotrophic energy metabolism.
ferrous iron example of inorganic electron donor rdfs:subClassOf
Fe(II) is an example inorganic electron donor for lithotrophic growth.
- DOI:10.1038/s41598-021-81412-3 Fe(II) as the energy source Supports Fe(II) oxidation as the energy source in engineered lithoheterotrophy.
inorganic electron donor feeds electrons into respiratory chain METPO:2007402
Oxidation of inorganic donors feeds respiratory electron transport.
- DOI:10.1016/j.bbabio.2008.09.008 membrane-bound electron transport chain Supports respiratory chains as energy-conserving redox systems.
respiratory chain transfers electrons to molecular oxygen METPO:2007403
Aerobic Fe(II)-oxidizing lithotrophy can reduce oxygen.
- DOI:10.1038/s41598-021-81412-3 oxidation of Fe(II) coupled to the reduction of oxygen Supports oxygen reduction coupled to Fe(II) oxidation.
respiratory chain has output ATP RO:0002234
Respiratory electron transport supports ATP synthesis.
- DOI:10.1016/j.bbabio.2008.09.008 drives ATP synthesis Supports ATP synthesis from respiratory energy conservation.
lithoheterotrophic has carbon source organic carbon METPO:2007806
Lithoheterotrophy uses organic compounds as carbon sources.
- DOI:10.1038/s41598-021-81412-3 glucose as the sole carbon source Supports organic carbon use under Fe(II)-oxidizing lithoheterotrophic conditions.
glucose example of organic carbon rdfs:subClassOf
Glucose is an experimentally supported organic carbon source.
- DOI:10.1038/s41598-021-81412-3 glucose as the sole carbon source Supports glucose as the organic carbon source in the engineered strain.
organic carbon converted to precursor metabolites
Organic carbon supplies biosynthetic precursors.
- DOI:10.1038/s41598-021-81412-3 biomass precursors provided by glucose Supports glucose-derived carbon as a source of biomass precursors.
precursor metabolites incorporated into biomass biolink:part_of
Organic-carbon precursors are incorporated into cellular material.
- DOI:10.1016/B978-012373944-5.00083-3 incorporation of a compound into biomass Supports assimilation of compounds into biomass.
microaerobic conditions supports Fe(II) oxidation
Microaerobic conditions support Fe(II)-oxidizing growth by limiting abiotic Fe(II) oxidation.
- DOI:10.1038/s41598-021-81412-3 requiring microaerobic conditions because atmospheric O2 abiotically oxidizes Fe(II)
ferrous iron oxidized in Fe(II) oxidation
Ferrous iron is the substrate oxidized in the energy-yielding Fe(II) oxidation process.
- DOI:10.1038/s41598-021-81412-3 the oxidation of Fe(II) coupled to the reduction of oxygen
Fe(II) oxidation feeds electrons into respiratory chain METPO:2007402
Fe(II) oxidation provides electrons for respiratory energy conservation.
- DOI:10.1038/s41598-021-81412-3 Fe(II) oxidation provides energy while organic carbon serves primarily as the carbon source
sulfide example of inorganic electron donor rdfs:subClassOf
Sulfide is an inorganic electron donor for lithotrophic sulfur oxidation.
- DOI:10.1038/s41467-025-56588-1 sulfide oxidation as lithotrophic energy metabolism in nitrate-reducing chemolithotrophs/heterotrophs
molecular hydrogen example of inorganic electron donor rdfs:subClassOf
H2 is a reduced inorganic donor that can supplement energy during organic-carbon-supported growth.
- DOI:10.1038/s41564-023-01322-0 uses an abundant reduced gas as an energy source The culture study shows that S. alaskensis consumes H2 while growing on organic carbon, supporting H2 as the inorganic energy donor in this branch.
molecular hydrogen oxidized by group 2a [NiFe]-hydrogenase
The group 2a uptake hydrogenase mediates aerobic H2 oxidation in S. alaskensis.
- DOI:10.1038/s41564-023-01322-0 encodes a plasmid-borne group 2a [NiFe]-hydrogenase, aerobically consumed H2 The primary growth, gas-consumption, and hucL-expression experiments pair the enzyme class with H2 oxidation in strain RB2256; Q1J422 is only its large-subunit component.
sulfide:quinone oxidoreductase (SQR) oxidizes sulfide METPO:2007803
SQR catalyzes oxidation/detoxification of sulfide as a sulfide-oxidation module.
- DOI:10.1038/s41467-025-56588-1 a key enzyme that can catalyze sulfide detoxification in nitrate-reducing chemolithoautotrophs
thiosulfate example of inorganic electron donor rdfs:subClassOf
Thiosulfate is an inorganic sulfur electron donor for lithotrophic oxidation.
- DOI:10.1038/s41467-025-56588-1 periplasmic sox gene clusters encoding for thiosulfate oxidation
periplasmic Sox system oxidizes thiosulfate METPO:2007803
The periplasmic Sox system encodes oxidation of thiosulfate.
- DOI:10.1038/s41467-025-56588-1 periplasmic sox gene clusters encoding for thiosulfate oxidation

Protein and taxon examples

Graph node Protein Taxon UniProt status Role and evidence

group 2a [NiFe]-hydrogenase

Graph node	Protein	Taxon	UniProt status	Role and evidence
group 2a [NiFe]-hydrogenase	`UniProtKB:Q1J422` Group 2a [NiFe]-hydrogenase large subunit HucL (Sala_3198)	Sphingopyxis alaskensis RB2256 `NCBITaxon:317655`	`UNREVIEWED` retrieved 2026-08-24 · entry v98 · sequence v1	Catalytic large-subunit component of the plasmid-borne group 2a [NiFe]-hydrogenase; this accession is not presented as the complete hydrogenase complex. `DOI:10.1038/s41564-023-01322-0` group 2a [NiFe]-hydrogenase large subunit gene (hucL; locus Sala_3198) The primary study measured Sala_3198 expression during aerobic growth and H2 oxidation. UniProtKB Q1J422 maps that exact locus to the S. alaskensis RB2256 reference proteome.

UniProtKB:Q1J422
Group 2a [NiFe]-hydrogenase large subunit HucL (Sala_3198)

Sphingopyxis alaskensis RB2256
NCBITaxon:317655

UNREVIEWED
retrieved 2026-08-24 · entry v98 · sequence v1

Catalytic large-subunit component of the plasmid-borne group 2a [NiFe]-hydrogenase; this accession is not presented as the complete hydrogenase complex.

DOI:10.1038/s41564-023-01322-0 group 2a [NiFe]-hydrogenase large subunit gene (hucL; locus Sala_3198) The primary study measured Sala_3198 expression during aerobic growth and H2 oxidation. UniProtKB Q1J422 maps that exact locus to the S. alaskensis RB2256 reference proteome.

Provenance

Identifier source: METPO (2026-06-12)
Author: Jed Dongjin Kim-Ozaeta
Definition source: DOI:10.1038/s41598-021-81412-3

Parent traits (1)

trophic type METPO:1000631

Synonyms (1)

lithoheterotroph RELATED_SYNONYM · metpo.owl

kg-microbe context

Matched 1 kg-microbe node via direct_metpo.

METPO:1000648 [-0.997, -3.520, -5.312, -0.246, …]

512-dim DeepWalkSkipGramEnsmallen embedding from kg-microbe (2026-04-25).

Nearest neighbors in embedding space

Top-8 cosine-similar METPO traits from the 2026-04-25 deepwalk (512-D).

physiology trophic type 0.838
physiology photolithoautotrophic 0.831
physiology lithoautotrophic 0.829
physiology hydrogenotrophic 0.827
physiology carboxydotrophic 0.825
physiology photoorganoheterotrophic 0.790
physiology chemoautotrophic 0.783
physiology mixotrophic 0.777

Deep research

Generated by just research-trait; source: research/traits/physiology/lithoheterotrophic-deep-research-falcon.md

Unreviewed literature output — not curated TraitMech content Ontology identifiers suggested below have not been resolved against their ontologies, and some are known to be wrong. Check any CURIE against the source before using it.

# Curation-focused research report: lithoheterotrophic

**Trait:** `lithoheterotrophic`
**Identifier:** **“METPO:1000648”**
**Category / kind / status:** PHYSIOLOGY / CLASS / REVIEWED
**Parent:** `METPO:1000631`

## 1. Scope summary and current understanding

Lithoheterotrophy is a trophic strategy in which oxidation of a reduced inorganic electron donor supplies respiratory energy, while preformed organic compounds provide the principal carbon incorporated into biomass. The defining evidence therefore requires two experimentally separable fluxes: **(i)** inorganic-donor oxidation linked to energy conservation and **(ii)** organic-carbon uptake and assimilation. It does not require one universal donor, acceptor, or pathway.

The clearest model is *Arcobacter peruensis*: sulfide oxidation is coupled to nitrate reduction, whereas acetate is assimilated and CO₂ fixation is negligible. The isolate grew best with sulfide, nitrate, and acetate; isotope experiments verified acetate assimilation and complete nitrate reduction to N₂. Its reported yield was 3.1 mol assimilated C per mol H₂S oxidized, and sulfide plus acetate supported approximately twice the growth observed under CO₂-fixing conditions. The organism’s acetate system had an apparent *K*m of 5.4 μM. These observations directly separate energy source from biomass-carbon source. (callbeck2019arcobacterperuensissp. pages 9-12)

A 2023 marine study broadened this model to trace-gas metabolism: H₂ oxidation by uptake [NiFe]-hydrogenases can supply enough energy for growth of otherwise heterotrophic bacteria, including *Sphingopyxis alaskensis*. The estimated H₂-derived cell-specific power was 5.4 × 10⁻¹³ W. Hydrogenase genes occurred across eight bacterial phyla and were expressed in ocean metatranscriptomes. (lappan2023molecularhydrogenin pages 6-7, lappan2023molecularhydrogenin pages 1-2)

### Boundaries

- **Versus chemolithoautotrophy:** both obtain energy from inorganic donors, but lithoautotrophs obtain biomass carbon primarily from CO₂/HCO₃⁻. Growth on H₂ plus CO₂ alone, for example, is not evidence for this trait. (zeng2021microorganismsfromdeepsea pages 9-11, zeng2021microorganismsfromdeepsea pages 12-13)
- **Versus chemoorganoheterotrophy:** if an organic compound supplies both electrons/energy and biomass carbon, the phenotype is organoheterotrophic unless an inorganic donor makes a demonstrated energetic contribution.
- **Versus mixotrophy:** “mixotrophy” is broader and inconsistently applied. It can include simultaneous organic-carbon assimilation and CO₂ fixation, or co-oxidation of organic and inorganic energy sources. Curate `METPO:1000648` only where organic carbon is the primary biomass source and inorganic oxidation contributes energy.
- **Maintenance versus growth:** CO oxidation is common, but the 2023 marine analysis concluded that CO generally supported survival during organic-carbon starvation, whereas H₂ produced enough power to support growth. CO oxidation alone should therefore not automatically imply lithoheterotrophic growth. (lappan2023molecularhydrogenin pages 6-7, lappan2023molecularhydrogenin pages 2-3)
- **Genotype versus phenotype:** `coxL`, hydrogenase, `sqr`, or `sox` genes indicate potential, not the complete trait. Expression, donor consumption, acceptor reduction, growth/yield, and organic-carbon assimilation provide stronger evidence.
- **Facultative status:** an organism can be lithoheterotrophic only under particular conditions and organoheterotrophic or lithoautotrophic under others. The graph should represent the assayed condition rather than impose an obligate lifestyle.

## 2. Candidate graph nodes

### Trait and process nodes

- lithoheterotrophic — **“METPO:1000648”**
- inorganic electron-donor oxidation
- organic-carbon assimilation
- aerobic respiration — `GO:0009060`
- nitrate respiration — `GO:0042126`
- denitrification — `GO:0019333`
- hydrogen oxidation
- carbon-monoxide oxidation
- sulfide oxidation
- thiosulfate oxidation
- acetate assimilation
- respiratory electron-transfer chain
- proton-motive-force generation
- ATP synthesis coupled to electron transport — `GO:0042773`
- cellular growth — `GO:0016049`

### Chemicals and environmental inputs

Conservative ChEBI candidates include:

- molecular hydrogen — `CHEBI:18276`
- carbon monoxide — `CHEBI:17245`
- carbon dioxide — `CHEBI:16526`
- dioxygen — `CHEBI:15379`
- nitrate — `CHEBI:17632`
- nitrite — `CHEBI:16301`
- hydrogen sulfide — `CHEBI:16136`
- thiosulfate — `CHEBI:26977`
- elemental sulfur — label-only pending choice of the intended sulfur allotrope/species
- iron(II) — `CHEBI:29033`
- acetate — `CHEBI:30089`
- glucose — `CHEBI:17234`

Showing the first 60 of 223 lines of findings; the linked file also carries the run's front matter and the prompt it was given — read the full report.

Canonical examples (1)

Organisms cited as exemplars of this trait. Taxon ids are NCBITaxon and link out to the NCBI record.

Sphingopyxis alaskensis RB2256 NCBITaxon:317655 DOI:10.1038/s41564-023-01322-0 Strain-level facultative lithoheterotrophic example that oxidizes H2 during aerobic growth on organic carbon, paired to its group 2a hydrogenase large subunit.

Curation history

2026-05-05T01:35:46.875356+00:00 · SEEDED_FROM_METPO · seed_from_metpo
imported from data/raw/metpo.owl (CLASS)
2026-05-09T00:00:00-07:00 · ADDED_CAUSAL_GRAPH · codex
Added DOI-backed causal graph for inorganic electron donor oxidation, Fe(II), respiratory energy conservation, organic carbon use, and biomass formation.
2026-05-20T03:35:31Z · GROUND_CAUSAL_PREDICATES · claude
Grounded 3 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv (METPO:2000009×1, METPO:2000202×1, METPO:2000006×1).
2026-05-23T08:21:50Z · GROUND_CAUSAL_PREDICATES · claude
Grounded 2 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv (rdfs:subClassOf×2).
2026-05-23T21:30:07Z · GROUND_CAUSAL_PREDICATES · claude
Grounded 2 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv (METPO:2007402×1, METPO:2007403×1).
2026-05-24T04:38:01Z · GROUND_CAUSAL_NODES · claude
Grounded 3 causal-node grounding field(s) via mappings/node_grounding.tsv (CHEBI:29033×1, CHEBI:50860×1, GO:0022904×1).
2026-05-24T04:41:04Z · GROUND_CAUSAL_NODES · claude
Grounded 2 causal-node grounding field(s) via mappings/node_grounding.tsv (METPO:1007502×1, METPO:1007501×1).
2026-05-24T07:34:59Z · RETYPE_CAUSAL_NODES · claude
Re-typed 1 causal-node node_type field(s) to align with CausalNodeTypeEnum semantics: biomass: BIOLOGICAL_PROCESS → CHEMICAL ×1.
2026-06-13T21:03:27Z · GROUND_CAUSAL_PREDICATES · claude
Grounded 1 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv (biolink:part_of×1).
2026-06-23T00:00:00Z · ENRICH_CAUSAL_GRAPH · claude
Added 8 evidence-backed generic edges (8 new nodes) from the deep-research report.
2026-06-24T17:21:14Z · GROUND_CAUSAL_PREDICATES · claude
Grounded 6 causal-edge predicate_id field(s) via mappings/predicate_grounding.tsv (rdfs:subClassOf×2, METPO:2000016×2, METPO:2007402×1, RO:0002327×1).
2026-06-24T17:21:20Z · GROUND_CAUSAL_NODES · claude
Grounded 2 causal-node grounding field(s) via mappings/node_grounding.tsv (CHEBI:15138×1, CHEBI:16094×1).
2026-07-20T04:23:55Z · GROUND_CAUSAL_NODES · claude
Grounded 1 causal-node grounding field(s) via mappings/node_grounding.tsv (GO:0070224×1).
2026-08-05T12:00:00Z · REVERSE_CAUSAL_EDGE_DIRECTION · claude
Reversed 1 causal edge from <trait> uses electron donor <chemical> to <chemical> enables <trait> (predicate_id METPO:2000009 -> RO:0002327), issue 295. METPO:2000009 is rdfs:subPropertyOf METPO:2000001, whose rdfs:domain is METPO:1000525 (microbe), so the trait-subject form entailed that this TRAIT node is a microbe; CausalNodeTypeEnum has no organism member, so no causal-graph edge can satisfy that domain. Evidence unchanged; only subject/predicate/object/predicate_id and the edge description moved. Note RO:0002327 has range 'biological process or activity', so the new form is not fully range-correct either - tracked in issue 302.
2026-08-06T00:00:00Z · MIGRATE_ENABLES_TRAIT_EDGES · claude
Migrated 1 causal edge(s) off enables/RO:0002327 with a TRAIT object (1 to has electron donor), issue 302. RO:0002327 has range 'biological process or activity', which a trait (a disposition) cannot satisfy, so the previous form entailed trait is-a BiologicalProcessOrActivity. The replacements are proposed in proposals/metpo_traitmech_v8 and are placeholder ids until METPO mints them. 1 electron edge(s) were also reversed back to trait -> chemical, restoring the donor/acceptor role that PR 300 collapsed onto enables (issue 303); the organism-subject problem that forced that collapse does not arise here because these predicates take a causal-node domain rather than METPO:2000001's microbe domain (issue 301).
2026-08-06T01:00:00Z · MIGRATE_MICROBE_DOMAIN_EDGES · claude
Re-grounded 2 causal edge(s) off microbe-domain METPO predicates (1 to has output, 1 to has carbon source), issue 301. The previous predicates are transitively rdfs:subPropertyOf METPO:2000001, whose rdfs:domain is METPO:1000525 (microbe), so a causal-graph subject entailed that the subject IS a microbe; CausalNodeTypeEnum has no organism member, so no such edge could ever satisfy the domain. Edge directions are unchanged - this pass only relabels and re-grounds. RO:0002234 (has output) is used where the subject is an activity, since biolink gives it the domain 'biological process or activity'; the METPO replacements are proposed in proposals/metpo_traitmech_v8 and v9 and are placeholder ids until METPO mints them.
2026-08-06T02:00:00Z · MIGRATE_MICROBE_DOMAIN_EDGES_PART2 · claude
Re-grounded 2 causal edge(s) off microbe-domain METPO predicates onto their causal-graph counterparts (2 to oxidizes), issue 301 part 2. The previous predicates are transitively rdfs:subPropertyOf METPO:2000001, whose rdfs:domain is METPO:1000525 (microbe), so a causal-graph subject entailed that the subject IS a microbe; CausalNodeTypeEnum has no organism member, so no such edge could ever satisfy the domain. Each replacement is a 1:1 mirror of its source predicate that changes only the domain, so the claim each edge makes is unchanged and directions are unchanged. The replacements are proposed in proposals/metpo_traitmech_v9 and are placeholder ids until METPO mints them.
2026-08-17T02:00:00Z · NORMALISE_NODE_SENSE · claude
One node_id per SENSE (issues 356, 384): molecular_oxygen is the chemical sense here. The molecule, not the condition — the dioxygen participating in the reaction the graph describes. Normalised onto molecular_oxygen, the id 20 other chemical occurrences already use, so one id means one sense corpus-wide (issues 356, 384).
2026-08-24T12:55:00-07:00 · REVIEWED_CAUSAL_GRAPH_PROTEIN_TAXON · codex
Marked the graph mechanistic, reviewed the Sox and conductive-surface composites as label-only, added DOI-cited S. alaskensis RB2256 and its H2 branch, and paired the group 2a hydrogenase with reference-proteome component Q1J422 without treating one large subunit as the complete complex.
2026-08-31T11:45:00Z · CONNECT_CAUSAL_GRAPH_COMPONENTS · codex
Resolved issue #183 graph fragmentation (2 components to 1): removed the disconnected, out-of-scope DIET island. No paid research service was called.